Bullous pemphigoid is an acquired autoimmune disease that is characterized by subepidermal blistering and affects mainly the elderly. The pathogenesis of the condition has not yet been fully elucidated, but it is widely accepted that a strong correlation with various medications may exist. In reality, more than 50 different drugs have been associated with the appearance of bullous pemphigoid and as new therapies emerge, this number is very likely to increase. A number of pathogenetic mechanisms have been proposed in the past. It is true that a delicate immunological balance is disturbed in all patients with the disease. The variable effects that may be exhibited by the use of biological drugs could shed some light in this complex immunological behaviour. At the same time, drug-induced bullous pemphigoid is difficult to differentially diagnose from its idiopathic counterpart, as the clinical picture and histopathological findings in both conditions may only have subtle differences. Patients who present with bullous pemphigoid and receive multiple regimens should always be suspected of suffering from the drug-induced variant of the condition. This possibility must be considered, as after the withdrawal of the suspect medication most patients respond rapidly to treatment and do not experience relapses.

Drug-induced pemphigoid: a review of the literature.

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Pemphigus and pemphigoid as paradigms of organ-specific, autoantibody-mediated diseases.

Background: Linear IgA bullous dermatosis (LABD) is an autoimmune subepidermal blistering disease that may be associated with drug exposure. Objective: Our purpose was to compare the clinical, pathologic, and immunofluorescence findings in drug-induced LABD with those in the idiopathic type. Methods: Six patients with an acute drug eruption were identified who had linear IgA deposition at the basement membrane zone (BMZ). Lesional tissue was examined by brightfield microscopy, and perilesional tissue was examined by direct immunofluorescence (DIF). The presence of circulating BMZ antibody was assayed by indirect immunofluorescence (IIF) on monkey esophagus (ME) and salt-split human skin (SS). Results: Histopathologic examination showed subepidermal bullae with varying numbers of inflammatory cells. DIF showed linear IgA at the BMZ; three of the patients also had weak deposition of C3 at the BMZ. Serum from five patients was studied by IIF. One patient had circulating IgA BMZ antibodies in a titer of 1:80 on ME, localized to the dermal side on SS. All patients were free of lesions within 5 weeks after discontinuation of the drug. Conclusion: Drug-induced LABD is a self-limited eruption characterized by linear deposition of IgA without IgG at the BMZ. Most patients lack circulating antibodies. The distribution of lesions and the course of the disease differ from those of idiopathic LABD.

Drug-induced linear IgA bullous dermatosis: Report of six cases and review of the literature

Background and Design: Bullous pemphigoid is the most frequent autoimmune blistering disease. It occurs in the elderly. The cause of this disease is unknown, but cases of bullous pemphigoid have been occasionally attributed to drug therapy. We conducted a multicenter prospective case-control study looking at the drugs used on a long-term basis before the onset of the disease in 116 incident cases of bullous pemphigoid and 216 control patients with malignant or benign skin tumors. Results: Case patients and control patients received many drugs on a long-term basis (mean ± SD, 4.4±3.2 and 4.4±2.7 years, respectively). Two classes of drugs, neu-n roleptics and diuretics, were used more frequently by case patients than control patients. Neuroleptics were used by 15.5% of case patients and 8.3% of control patients (adjusted odds ratios, 1.9; 95% confidence interval, 0.95 to 3.8). Diuretics were used by 36.2% of case patients and 24.5% of control patients (adjusted odds ratios, 1.8; 95% confidence interval, 1.1 to 2.9). Among neuroleptics, no specific drug emerged. The association with diuretics was only linked to aldosterone antagonists, which were taken by 12.9% of case patients and 4.6% of control patients (adjusted odds ratios, 3.1; 95% confidence interval, 1.4 to 7.1). Conclusions: These results suggest that some drug therapies may be a risk factor for bullous pemphigoid. The cause of this association should be further investigated. (Arch Dermatol. 1996;132:272-276)

Drugs Associated With Bullous Pemphigoid: A Case-Control Study

https://www.cidjournal.com/article/S0738-081X(13)00007-2/pdf

Bullous pemphigoid: etiology, pathogenesis, and inducing factors: facts and controversies

The consumption of drugs is increasing worldwide. The greater it becomes, the more we have to reckon with cutaneous side effects. Lately, bullous drug eruptions have seemed to predominate over others; this may be connected with the widespread use of potent new drugs that, in certain conditions, prove to be capable of causing intraepidermal or dermo-epidermal detachment. This review focuses on two serious bullous drug reactions that more and more frequently have appeared in recent dermatologic reports: pemphigus and bullous pemphigoid.

Guido Sacerdoti

Papers

Pemphigus and bullous pemphigoid due to drugs.